AIM:To determine the optimal dosage and mechanism of Ginkgolide B(BN52021) on severe acute pancreatitis(SAP) of rats.METHODS:Seventy male Wistar rats were randomly divided into seven groups(10 for each group).Shamoper...AIM:To determine the optimal dosage and mechanism of Ginkgolide B(BN52021) on severe acute pancreatitis(SAP) of rats.METHODS:Seventy male Wistar rats were randomly divided into seven groups(10 for each group).Shamoperation group(SO),SAP model group(SAP),dimethyl sulfoxide(DMSO) contrast group(DMSO),and groups treated with 2.5 mg/kg BN52021(BN1),5 mg/kg BN52021(BN2),10 mg/kg BN52021(BN3),and 20 μg/kg Sandostatin(SS).The SAP model was established in Wistar rats by injecting 5% sodium taurocholate retrogradely into the common bilio-pancreatic duct.The rats of SO,DMSO and BN52021 were injected with 0.9% NaCl,0.5% DMSO and BN52021 through femoral vein 15 min after the operation.The SS group was injected with Sandostatin subcutaneously.All rats were anaesthetized at 6 h after operation,and venous blood was collected to determine the levels of serum amylase and phospholipase A2(PLA2),and pancreas tissue was harvested and stained.RESULTS:There was no significant difference between the SAP and DMSO groups in serum amylase level,PLA2,ascites and pathologic score,but significant difference was found in SAP/DMSO groups compared with those in SO group(P < 0.05) and the levels of serum amylase,PLA2,ascites,and pathologic score were lower in the BN1,BN2,BN3 and SS groups than in the SAP and DMSO groups(P < 0.05).However,among BN1,BN2,BN3 and SS groups,BN2 had the best effect in decreasing the levels of serum amylase and PLA2(P < 0.05).Expression of platelet activating factor(PAF) receptor(PAFR) mRNA and protein showed no significant difference between the SAP and DMSO groups,or among BN1,BN2,BN3 and SS groups,but there was remarkable difference between SAP/DMSO group and SO group(P < 0.05),and expression of PAFR mRNA and protein was higher in the BN1,BN2,BN3 and SS groups than in the SAP and DMSO groups(P < 0.05).PAFR expression was observed in the nucleus and cytoplasm of pancreatic islet cells in Wistar rats by immunohistochemistry.CONCLUSION:By iv injection,5 mg/kg of BN52021 is the optimal dosage for SAP rats.BN52021 may inhibit the interaction/binding of PAF with PAFR.展开更多
Objective: To observe the therapeutic effect of different dosages of Gegen Qin Lian Decoction (葛根芩连汤) on type 2 diabetic patients. Methods: Fifty-four type 2 diabetic patients from low dosage group (20 cases), me...Objective: To observe the therapeutic effect of different dosages of Gegen Qin Lian Decoction (葛根芩连汤) on type 2 diabetic patients. Methods: Fifty-four type 2 diabetic patients from low dosage group (20 cases), medium dosage group (19 cases) and high dosage group (15 cases) were treated with different dosage of Gegen Qin Lian Decoction for 12 weeks. Fasting blood-glucose (FBG), postprandial blood sugar (PBG) and Hemoglobin A1c (HbAlc) were determined before and after treatment. Results: With the increase of dosage, the overall effective rate of glycaemic control increased, and FBG, PBG, HbAlc decreased. The overall effective rate of blood glucose control of high dosage, medium dosage and low dosage group were 80%, 47%, 30% respectively, and there were significant differences between high dosage group and low dosage group. The decrease of FBG, PBG and HbAlc of high dosage showed significant differences from low dosage too. These data was analyzed by trend χ2 test and covariance analysis. Conclusion: The result indicated that different dosage of Gegen Qin Lian Decoction has dose-effect relationship in reducing HbAlc and FBG.展开更多
We discuss here the complexity of the doses of traditional Chinese medicine(TCM) prescriptions and herbs from different viewpoints,including the heterogeneity of drug quality,the flexibility of prescriptions,and the d...We discuss here the complexity of the doses of traditional Chinese medicine(TCM) prescriptions and herbs from different viewpoints,including the heterogeneity of drug quality,the flexibility of prescriptions,and the diversity of drug effects.Then,the corresponding research ideas and strategies are proposed.We can reveal the actual situation of clinical doses based on in-depth "real-world study" of the safety and effectiveness of TCM prescriptions,create an analytical method for dose-effect relationships in accordance with the features of TCM,and reveal the correlated regular nature of the effectiveness and dosage of TCM prescriptions and herbs.展开更多
In order to prevent severe pollution by de-icing salt on greenery along urban roads, a half lethal dose （LD_50）for a plant population was confirmed through stress simulation of chloride de-icing salt on Euonymus jap...In order to prevent severe pollution by de-icing salt on greenery along urban roads, a half lethal dose （LD_50）for a plant population was confirmed through stress simulation of chloride de-icing salt on Euonymus japonicus, with an ianalysis of physiological changes, statistics on mortality rate on plant populations and mathematic modeling during a 30- day subacute toxicity test. The results indicate that a significant positive correlation in the early stages and a significant negative correlation in the later stages were observed between the amount of chlorophyll a and b in plants and a cumulative dose of de-icing salt. The amounts of free proline in plants and the dose of de-icing salt were positively correlated Over the entire period. No significant correlation in the initial stage, but a significant negative correlation in later stages was observed between the soluble protein and the dose of de-icing salt. LDs0 of this chloride agent on E. japonicus is 5 kg.（L·m2）-1 over 30 days.展开更多
Aim To evaluate the time-effect and dose-effect of prasugrel hydrobromide acetic acid compound （PHAAC） inhibiting platelet aggregation. Methods For the time-effect study, 190 Sprague-Dawley （SD） rats were devided ...Aim To evaluate the time-effect and dose-effect of prasugrel hydrobromide acetic acid compound （PHAAC） inhibiting platelet aggregation. Methods For the time-effect study, 190 Sprague-Dawley （SD） rats were devided into 19 groups （n- 10）： the vehicle control group, the PHAAC groups （0.5, 1, 2, 4, 6, 24, 48, 72, 96 h） and the prasugrel hydrochloride groups （0.5, 1, 2, 4, 6, 24, 48, 72, 96 h）. Rats were singly intra- gastic administration of the vehicle, the PHAAC （5 mg·kg^-1） or the prasugrel hydrochloride （5 mg · kg^-1 ）, re- spectively. Blood samples were taken at each time point for the determination of platelet aggregation rate （PAR）. For the dose-effect study, 110 SD rats were devided into 11 groups （n= 10）： the vehicle control group, the PHAAC groups （10, 5, 2.5, 1, 0.5 mg · kg^-1, dosage of prasugrel） and the prasugrel hydrochloride groups （ 10, 5, 2.5, 1, 0.5 mg · kg^-1, dosage of prasugrel） . Blood samples were taken at 4 h after drug administration for the determination of PAR. Results Compared with the vehicle group, PHAAC has significant anti-platelet ag- gregative effects （P 〈 0.05） at the time of 0.5, 1, 2, 4, 6, 24, 48 h, and the effect at the time of 4 h was the strongest. There were no obvious differences between the effect of PHAAC （5 mg · kg^-1） and prasugrel hydrochlo- ride （5 mg · kg^-1） at each time point. Compared with the vehicle group, intragastic administration of PHAAC at the doses of 10, 5, 2.5, 1, 0.5 mg · kg^-1 could obviously inhibite the platelet aggregation, and showed a dose- dependent manner. There were no significant differences between the effect of PHAAC and prasugrel hydrochloride at the same dose. Conclusion PHAAC can inhibit platelet aggregation in a dose-dependent manner, and the effect at 4 h after drug administration is the strongest. The action strength and duration of PHAAC are similar with that of the prasugrel hydrochloride.展开更多
Objective:To calculate the focus absorption dose of 153Sm-EDTMP with the Monte Carlo(MC)EGS4 method for treatment of bone metastases from nasopharyngeal carcinoma or breast cancer,and investigate the relationship betw...Objective:To calculate the focus absorption dose of 153Sm-EDTMP with the Monte Carlo(MC)EGS4 method for treatment of bone metastases from nasopharyngeal carcinoma or breast cancer,and investigate the relationship between the focus absorption dose and painkilling effect of 153Sm-EDTMP.Methods:Four patients with multiple bone metastases from nasopharyngeal or breast carcinoma and suffered from grade IV bone pain were treated with radionuclide internal irradiation of 153Sm-EDTMP.The absorption dose and dose distribution of bone metastases and other targeted organs were calculated with MC EGS4 program based on the time-order SPECT/CT scanning and the measurement of the radioactivity in the urine accumulation.The release of bone pain and the improvement of life quality were observed.Results:Bone pain of the patients was significantly alleviated to grade II for 3–4 weeks after internal 153Sm-EDTMP irradiation.The 3-dimensional absorption dose distribution image of bone metastases and targeted organs showed that the dose distribution in bone metastases was not asymmetrical.After injection of 0.65×37 MBq/kg 153Sm-EDTMP,the highest absorption dose in bone lesions was about 4.9–5.9 Gy,and the dose in the lesion margin was about 2.0 Gy.Using the highest dose as reference dose point,the relative absorption dose values of bone marrow,vertebra and sex organ near lesions were 0.48–1.1 Gy,0.51–0.85 Gy,and 0.01–0.14 Gy,respectively.Conclusion:The absorption dose of bone metastases is significantly lower than treatment dose of 30 Gy after single irradiation of 153Sm-EDTMP.The painkilling effect is limited and in accordance with clinical observation.展开更多
The research on the dose-effect relationship in Chinese materia medica is delayed due to the complexity of its composition, multi-efficacy, multi-targeting and other factors. Many experts put forward re...The research on the dose-effect relationship in Chinese materia medica is delayed due to the complexity of its composition, multi-efficacy, multi-targeting and other factors. Many experts put forward relevant research ideas and methods and worked out more and more research results in literature, experimental and clinical categories because of the progress of statistical methods and scientific and technological means in recent years. In this paper, these results were preliminarily combed to show the basic situation of dose-effect relationship research in Chinese materia medica.展开更多
Objective To explore the velocity-effect relationship in order to the establish linearization of effect on an equation with regard to the consistency of the Hill dose-effect expression with the metabolic kinetics of r...Objective To explore the velocity-effect relationship in order to the establish linearization of effect on an equation with regard to the consistency of the Hill dose-effect expression with the metabolic kinetics of receptors.Methods The linear velocity-effect expression was obtained by solving multivariant differential equation groups,which were established to compare the coincidences and basic relations between the Hill dose-effect and metabolic kinetic Michaelis-Menten equation for receptors.The validation test was conducted with acetylcholine,adrenaline,and their mixture as model drugs.Results The linear velocity-effect modelling was represented in vivo or in vitro,for single and multidrug systems.Pharmacodynamic parameters,especially suitable for multicomponent CMM formulas,could be determined and calculated for single or multicomponent formulas at high saturating or low linear concentration for receptors.The validation test showed that the pharmacodynamic parameters of acetylcholine were:k,2.675×10^-3s^-1;ka,5.786×10^-9s^-1;km,2.500×10^-7s^-1;α,4.619×10^9张s·mg^-1;E0,13张(P<0.01)and those of adrenaline were:k,1.415×10^-3s^-1;ka,5.846×10^-9s^-1;km,2.300×10^-7s^-1;α,-1.627×10^9张s·m g^-1;E0,9.2张(P<0.01).For the mixture of the two components,the values were:α,1.375×1010张s·m g^-1;-6.150×10^9张s m g^-1for acetylcholine and adrenaline,respectively,and E0was7.08张in both,with the other parameters unchanged(P<0.01).Conclusion The velocity-effect equation can linearize the Hill dose-effect relationship,which can be applied to study the pharmacodynamics and availability of CMM formulations in vivo and in vitro.展开更多
基金Supported by Two grants from National Natural Science Foundation of China,No. 30300465 and No. 30772883
文摘AIM:To determine the optimal dosage and mechanism of Ginkgolide B(BN52021) on severe acute pancreatitis(SAP) of rats.METHODS:Seventy male Wistar rats were randomly divided into seven groups(10 for each group).Shamoperation group(SO),SAP model group(SAP),dimethyl sulfoxide(DMSO) contrast group(DMSO),and groups treated with 2.5 mg/kg BN52021(BN1),5 mg/kg BN52021(BN2),10 mg/kg BN52021(BN3),and 20 μg/kg Sandostatin(SS).The SAP model was established in Wistar rats by injecting 5% sodium taurocholate retrogradely into the common bilio-pancreatic duct.The rats of SO,DMSO and BN52021 were injected with 0.9% NaCl,0.5% DMSO and BN52021 through femoral vein 15 min after the operation.The SS group was injected with Sandostatin subcutaneously.All rats were anaesthetized at 6 h after operation,and venous blood was collected to determine the levels of serum amylase and phospholipase A2(PLA2),and pancreas tissue was harvested and stained.RESULTS:There was no significant difference between the SAP and DMSO groups in serum amylase level,PLA2,ascites and pathologic score,but significant difference was found in SAP/DMSO groups compared with those in SO group(P < 0.05) and the levels of serum amylase,PLA2,ascites,and pathologic score were lower in the BN1,BN2,BN3 and SS groups than in the SAP and DMSO groups(P < 0.05).However,among BN1,BN2,BN3 and SS groups,BN2 had the best effect in decreasing the levels of serum amylase and PLA2(P < 0.05).Expression of platelet activating factor(PAF) receptor(PAFR) mRNA and protein showed no significant difference between the SAP and DMSO groups,or among BN1,BN2,BN3 and SS groups,but there was remarkable difference between SAP/DMSO group and SO group(P < 0.05),and expression of PAFR mRNA and protein was higher in the BN1,BN2,BN3 and SS groups than in the SAP and DMSO groups(P < 0.05).PAFR expression was observed in the nucleus and cytoplasm of pancreatic islet cells in Wistar rats by immunohistochemistry.CONCLUSION:By iv injection,5 mg/kg of BN52021 is the optimal dosage for SAP rats.BN52021 may inhibit the interaction/binding of PAF with PAFR.
基金supported by a grant from the National Basic Research Program (973 Program, No.2010CB530601)
文摘Objective: To observe the therapeutic effect of different dosages of Gegen Qin Lian Decoction (葛根芩连汤) on type 2 diabetic patients. Methods: Fifty-four type 2 diabetic patients from low dosage group (20 cases), medium dosage group (19 cases) and high dosage group (15 cases) were treated with different dosage of Gegen Qin Lian Decoction for 12 weeks. Fasting blood-glucose (FBG), postprandial blood sugar (PBG) and Hemoglobin A1c (HbAlc) were determined before and after treatment. Results: With the increase of dosage, the overall effective rate of glycaemic control increased, and FBG, PBG, HbAlc decreased. The overall effective rate of blood glucose control of high dosage, medium dosage and low dosage group were 80%, 47%, 30% respectively, and there were significant differences between high dosage group and low dosage group. The decrease of FBG, PBG and HbAlc of high dosage showed significant differences from low dosage too. These data was analyzed by trend χ2 test and covariance analysis. Conclusion: The result indicated that different dosage of Gegen Qin Lian Decoction has dose-effect relationship in reducing HbAlc and FBG.
基金Supported by Scientific Research Special Project of TCM Profession (200907001E)Science and Technology Special Major Project for "Significant New Drugs Formulation"(2009ZX09301-005)
文摘We discuss here the complexity of the doses of traditional Chinese medicine(TCM) prescriptions and herbs from different viewpoints,including the heterogeneity of drug quality,the flexibility of prescriptions,and the diversity of drug effects.Then,the corresponding research ideas and strategies are proposed.We can reveal the actual situation of clinical doses based on in-depth "real-world study" of the safety and effectiveness of TCM prescriptions,create an analytical method for dose-effect relationships in accordance with the features of TCM,and reveal the correlated regular nature of the effectiveness and dosage of TCM prescriptions and herbs.
基金financially supported by the Science Innovation Project of Beijing Forestry University (No. 101305)the 985 Innovation Platform, China
文摘In order to prevent severe pollution by de-icing salt on greenery along urban roads, a half lethal dose （LD_50）for a plant population was confirmed through stress simulation of chloride de-icing salt on Euonymus japonicus, with an ianalysis of physiological changes, statistics on mortality rate on plant populations and mathematic modeling during a 30- day subacute toxicity test. The results indicate that a significant positive correlation in the early stages and a significant negative correlation in the later stages were observed between the amount of chlorophyll a and b in plants and a cumulative dose of de-icing salt. The amounts of free proline in plants and the dose of de-icing salt were positively correlated Over the entire period. No significant correlation in the initial stage, but a significant negative correlation in later stages was observed between the soluble protein and the dose of de-icing salt. LDs0 of this chloride agent on E. japonicus is 5 kg.（L·m2）-1 over 30 days.
文摘Aim To evaluate the time-effect and dose-effect of prasugrel hydrobromide acetic acid compound （PHAAC） inhibiting platelet aggregation. Methods For the time-effect study, 190 Sprague-Dawley （SD） rats were devided into 19 groups （n- 10）： the vehicle control group, the PHAAC groups （0.5, 1, 2, 4, 6, 24, 48, 72, 96 h） and the prasugrel hydrochloride groups （0.5, 1, 2, 4, 6, 24, 48, 72, 96 h）. Rats were singly intra- gastic administration of the vehicle, the PHAAC （5 mg·kg^-1） or the prasugrel hydrochloride （5 mg · kg^-1 ）, re- spectively. Blood samples were taken at each time point for the determination of platelet aggregation rate （PAR）. For the dose-effect study, 110 SD rats were devided into 11 groups （n= 10）： the vehicle control group, the PHAAC groups （10, 5, 2.5, 1, 0.5 mg · kg^-1, dosage of prasugrel） and the prasugrel hydrochloride groups （ 10, 5, 2.5, 1, 0.5 mg · kg^-1, dosage of prasugrel） . Blood samples were taken at 4 h after drug administration for the determination of PAR. Results Compared with the vehicle group, PHAAC has significant anti-platelet ag- gregative effects （P 〈 0.05） at the time of 0.5, 1, 2, 4, 6, 24, 48 h, and the effect at the time of 4 h was the strongest. There were no obvious differences between the effect of PHAAC （5 mg · kg^-1） and prasugrel hydrochlo- ride （5 mg · kg^-1） at each time point. Compared with the vehicle group, intragastic administration of PHAAC at the doses of 10, 5, 2.5, 1, 0.5 mg · kg^-1 could obviously inhibite the platelet aggregation, and showed a dose- dependent manner. There were no significant differences between the effect of PHAAC and prasugrel hydrochloride at the same dose. Conclusion PHAAC can inhibit platelet aggregation in a dose-dependent manner, and the effect at 4 h after drug administration is the strongest. The action strength and duration of PHAAC are similar with that of the prasugrel hydrochloride.
基金grants from the Key Sci-Tech Research Foundationof Guangzhou City(No.2002XZ-J200131)Natural Science Foundationof Guangdong Province(No.031563)National Natural ScienceFoundation(No.10675175).
文摘Objective:To calculate the focus absorption dose of 153Sm-EDTMP with the Monte Carlo(MC)EGS4 method for treatment of bone metastases from nasopharyngeal carcinoma or breast cancer,and investigate the relationship between the focus absorption dose and painkilling effect of 153Sm-EDTMP.Methods:Four patients with multiple bone metastases from nasopharyngeal or breast carcinoma and suffered from grade IV bone pain were treated with radionuclide internal irradiation of 153Sm-EDTMP.The absorption dose and dose distribution of bone metastases and other targeted organs were calculated with MC EGS4 program based on the time-order SPECT/CT scanning and the measurement of the radioactivity in the urine accumulation.The release of bone pain and the improvement of life quality were observed.Results:Bone pain of the patients was significantly alleviated to grade II for 3–4 weeks after internal 153Sm-EDTMP irradiation.The 3-dimensional absorption dose distribution image of bone metastases and targeted organs showed that the dose distribution in bone metastases was not asymmetrical.After injection of 0.65×37 MBq/kg 153Sm-EDTMP,the highest absorption dose in bone lesions was about 4.9–5.9 Gy,and the dose in the lesion margin was about 2.0 Gy.Using the highest dose as reference dose point,the relative absorption dose values of bone marrow,vertebra and sex organ near lesions were 0.48–1.1 Gy,0.51–0.85 Gy,and 0.01–0.14 Gy,respectively.Conclusion:The absorption dose of bone metastases is significantly lower than treatment dose of 30 Gy after single irradiation of 153Sm-EDTMP.The painkilling effect is limited and in accordance with clinical observation.
文摘The research on the dose-effect relationship in Chinese materia medica is delayed due to the complexity of its composition, multi-efficacy, multi-targeting and other factors. Many experts put forward relevant research ideas and methods and worked out more and more research results in literature, experimental and clinical categories because of the progress of statistical methods and scientific and technological means in recent years. In this paper, these results were preliminarily combed to show the basic situation of dose-effect relationship research in Chinese materia medica.
基金funding support from the National Natural Science Foundation of China (No. 81073142 and No. 30901971)
文摘Objective To explore the velocity-effect relationship in order to the establish linearization of effect on an equation with regard to the consistency of the Hill dose-effect expression with the metabolic kinetics of receptors.Methods The linear velocity-effect expression was obtained by solving multivariant differential equation groups,which were established to compare the coincidences and basic relations between the Hill dose-effect and metabolic kinetic Michaelis-Menten equation for receptors.The validation test was conducted with acetylcholine,adrenaline,and their mixture as model drugs.Results The linear velocity-effect modelling was represented in vivo or in vitro,for single and multidrug systems.Pharmacodynamic parameters,especially suitable for multicomponent CMM formulas,could be determined and calculated for single or multicomponent formulas at high saturating or low linear concentration for receptors.The validation test showed that the pharmacodynamic parameters of acetylcholine were:k,2.675×10^-3s^-1;ka,5.786×10^-9s^-1;km,2.500×10^-7s^-1;α,4.619×10^9张s·mg^-1;E0,13张(P<0.01)and those of adrenaline were:k,1.415×10^-3s^-1;ka,5.846×10^-9s^-1;km,2.300×10^-7s^-1;α,-1.627×10^9张s·m g^-1;E0,9.2张(P<0.01).For the mixture of the two components,the values were:α,1.375×1010张s·m g^-1;-6.150×10^9张s m g^-1for acetylcholine and adrenaline,respectively,and E0was7.08张in both,with the other parameters unchanged(P<0.01).Conclusion The velocity-effect equation can linearize the Hill dose-effect relationship,which can be applied to study the pharmacodynamics and availability of CMM formulations in vivo and in vitro.
